Stable pharmaceutical compositions of mesalamine

Abstract

The present invention relates to stable pharmaceutical compositions of mesalamine. The composition of the invention is a capsule dosage form filled with a tablet. The invention also relates to process for preparing such compositions. The invention specifically relates to a composition of mesalamine wherein the composition is devoid of any reducing sugar or sugar alcohol.

1 . A stable pharmaceutical composition comprising:
 (a) a hard gelatin capsule shell; and   (b) at least one tablet within the capsule shell, wherein the tablet comprises mesalamine and one or more pharmaceutically acceptable excipients,   
       wherein the composition is devoid of any reducing sugar or sugar alcohol. 
     
     
         2 . The stable pharmaceutical composition according to  claim 1 , wherein the composition is substantially free of 5-[2-formyl-5-hydroxymethyl-1H-pyrrol-1-yl]-2-hydroxybenzoic acid upon storage of the composition at a relative humidity of 60% and a temperature of 25° C. for a period of at least six months. 
     
     
         3 . The stable pharmaceutical composition according to  claim 1 , wherein the tablet contains an enteric coat that prevents release of the mesalamine in the upper gastrointestinal tract. 
     
     
         4 . The stable pharmaceutical composition according to  claim 3 , wherein the enteric coat comprises poly(methacrylic acid, methyl methacrylate) at a ratio of about 1:2, poly(methacrylic acid, methyl methacrylate) at a ratio of about 1:1, or a mixture thereof. 
     
     
         5 . The stable pharmaceutical composition according to  claim 1 , wherein the capsule shell has more than about 10% by weight moisture content at a relative humidity of 60% and a temperature of 25° C. 
     
     
         6 . The stable pharmaceutical composition according to  claim 1 , wherein the tablet comprises from about 200 mg to about 1200 mg of mesalamine. 
     
     
         7 . The stable pharmaceutical composition according to  claim 1 , wherein the mesalamine has a bulk density of between about 0.3 g/ml and 0.8 g/ml. 
     
     
         8 . The stable pharmaceutical composition according to  claim 1 , wherein the tablet is greater than 5 mm in diameter. 
     
     
         9 . The stable pharmaceutical composition according to  claim 1 , wherein the capsule shell contains one tablet. 
     
     
         10 . The stable pharmaceutical composition according to  claim 1 , wherein the reducing sugar comprises one or more of lactose, maltose, galactose, glucose, fructose, ribose and xylose. 
     
     
         11 . The stable pharmaceutical composition according to  claim 1 , wherein the sugar alcohol comprises one or more of glycerol, erythritol, threitol, xylitol, ribitol, mannitol, sorbitol, galactitol, fucitol, iditol, isomalt, maltitol, and lactitol. 
     
     
         12 . A stable pharmaceutical composition of mesalamine comprising a hard gelatin capsule shell and at least one tablet within the capsule shell; wherein the composition is devoid of any reducing sugar or sugar alcohol; and when administered as two capsules three times daily for six days provides an in-vivo plasma profile for mesalamine with a mean of C max  ranging from 1 μg/mL to 9 μg/mL, a mean of AUC 0-t  ranging from 6 μg*hr/mL to 34 μg*hr/mL; and a mean of T max  ranging from 10 to 16 hours. 
     
     
         13 . A stable pharmaceutical composition of mesalamine comprising a hard gelatin capsule shell and at least one tablet within the capsule shell; wherein the composition is devoid of any reducing sugar or sugar alcohol; and when administered as two capsules three times daily for six days provides an in-vivo plasma profile for the active metabolite N-acetyl-5-aminosalicylic acid with a mean of C max  ranging from 2 μg/mL to 7 μg/mL, a mean of AUC 0-t  ranging from 14 μg*hr/mL to 36 μg*hr/mL; and a mean of T max  ranging from 10 to 16 hours. 
     
     
         14 . A kit comprising:
 the stable pharmaceutical composition according to  claim 1 ; and   a predetermined amount of desiccant.   
     
     
         15 . The kit according to  claim 14 , wherein the desiccant is silica gel.